A pilot study to assess the effects of combining fluticasone propionate/salmeterol and tiotropium on the airflow obstruction of patients with severe-to-very severe COPD

Abstract

A c c e p t e d m a n u s c r i p t AbstractThe aim of this pilot study was to explore the relative efficacy in terms of improvement in symptoms and lung function of combining fluticasone propionate/salmeterol combination (FSC) and tiotropium in patients with severe-to-very severe stable COPD. Ninety patients were randomized to receive 3 months of treatment in one of three treatment groups: (1) FSC 500/50 µg Diskus, 1 inhalation twice daily + placebo Handihaler 1 inhalation once-daily daily; (2) tiotropium 18 µg Handihaler, 1 inhalation once daily + placebo Diskus, 1 inhalation twice daily; (3) FSC 500/50 µg Diskus, 1 inhalation twice daily + tiotropium 18 µg Handihaler, 1 inhalation once-daily daily. Patients attended the clinic before and after 1 month, 2 months, and 3 months of treatment for evaluations of pulmonary function, and dyspnea, which was assessed using a visual analog scale (VAS). Also the supplemental salbutamol use was measured. Eighty-one patients completed the 3-month treatment period: 26 patients receiving FSC, 26 patients receiving tiotropium, and 29 patients receiving FSC + tiotropium. Patients were withdrawn for COPD exacerbation. Improvements in trough FEV 1 with all treatments medications were observed by the first month when trough FEV 1 had improved significantly above baseline by 74 mL (p < 0.05) in the tiotropium group, by 117 mL (p < 0.05) in the FSC group and by 115 mL (p < 0.05) in FSC + tiotropium group. At the end of the study, trough FEV1 had improved significantly above baseline by141 mL (p < 0.05) in the tiotropium group, by 140 mL (p < 0.05) in the FSC group and by 186 mL (p < 0.05) in FSC + tiotropium group. The difference between FSC and tiotropium appeared to decrease, that between FSC and FSC + tiotropium appeared to increase and that between tiotropium and FSC + tiotropium remained almost similar with study duration. Our results suggest that adding FSC and tiotropium may provide benefits in symptomatic patients with severe-to-very severe stable COPD.

Effects of Tiotropium and Salmeterol/Fluticasone Propionate on Airway Wall Thickness in Chronic Obstructive Pulmonary Disease

“…FEV 1 findings confirmed the superiority of Tio plus SFC therapy and agree with the findings of recent studies [13,14,15]. Singh et al [15] demonstrated that triple therapy improves a range of pulmonary function measurements, including not only FEV 1 and FVC but also IC.…”

“…Triple combination therapy with anticholinergics, ICS and LABA is widely used in clinical practice. This treatment approach is of interest because the goal of COPD management is to achieve optimal control, and with different mechanisms of action, there is reasonably good evidence to show that use of the 3 drugs in combination provides clinical benefits [13,14,15]. Treatment with the long-acting anticholinergic tiotropium (Tio) and salmeterol/fluticasone propionate combination (SFC) is therefore an attractive alternative for patients with more severe disease.…”

“…Cross-sectional studies have shown that CT indices that quantify airway wall thickening and emphysema are correlated with pulmonary function measurements [16,17,21,22]. The combination of Tio plus SFC has been shown to be more effective than either treatment alone in terms of improving pulmonary function [13,14,15]. However, there is little evidence that Tio plus SFC affects airway dimensions in COPD patients.…”

Superiority of "triple" therapy with salmeterol/fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD

“…16 Additionally, a pilot study in patients with severe COPD showed a benefit for triple therapy over SFC alone and TIO alone for pre-dose morning FEV 1 at 3 months. 17 A formal power calculation for this pilot study does not appear to have been performed, and the authors state that false negative results for lung function changes at earlier time points may be attributed to insufficient statistical power. Properly statistically powered studies are needed to fully define the pulmonary function advantages of triple therapy when compared with SFC alone and TIO alone.…”

The role of combination inhaled corticosteroid/long-acting β-agonist therapy in COPD management

“…Additional benefits in lung function may be gained with the addition of an inhaled long-acting anticholinergic agent to ICS/LABA therapy. 9,[23][24][25] Randomised controlled studies have found greater improvements in spirometric measures, as well as improved quality of life and reduced exacerbations, when ICS/LABA was added to tiotropium compared to either ICS/LABA or tiotropium alone. 9,[23][24][25] With increased interest in combination therapy, it can be anticipated that more trials will be conducted to clarify the relative effects of various drug regimens on lung function and other markers of COPD.…”